DISPOSITION AND METABOLISM OF [2-C-14]EPICHLOROHYDRIN AFTER ORAL-ADMINISTRATION TO RATS

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (3) , 333-341
Abstract
A comprehensive disposition and metabolism study of epichlorohydrin (ECH) was not previously reported. In this study, male Fischer 344 rats were doses (6 mg/kg) orally with [2-14C]ECH (98% radiochemically pure) as an aqueous solution and killed after 3 days. Approximately 38% of the radioactive dose was exhaled as CO2, 50% was excreted as metabolites in the urine and 3% was present in the feces. Radioactivity in tissues accounted for the remainder of the administered dose. When expressed per g of tissue, radioactivity was highest in liver, kidney and forestomach. The half-life of initial elimination of radioactivity in both the urine and exhaled air was .apprx. 2 h, indicating that ECH was rapidly absorbed and metabolized. The major metabolites in the urine were identified as N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine and .alpha.-chlorohydrin, about 36 and 4% of the administered dose, respectively. Finding these metabolites, which were not previously reported, is consistent with the initial metabolic reactions being conjugation of the epoxide with glutathione and hydration of the epoxide.